tbuckley/cabot-search huggingface dataset:
Cardiac Aging Is Promoted by Pseudohypoxia Increasing p300-Induced Glycolysis
Authors: Simone Serio, Christina Pagiatakis, Elettra Musolino, Arianna Felicetta, Pierluigi Carullo, Javier Laura Frances, Laura Papa, Giacomo Rozzi, Nicolò Salvarani, Michele Miragoli, Rosalba Gornati, Giovanni Bernardini, Gianluigi Condorelli, Roberto Papait
Journal: Circulation Research (2023)

Heart failure is typical in the elderly. Metabolic remodeling of cardiomyocytes underlies inexorable deterioration of cardiac function with aging: glycolysis increases at the expense of oxidative phosphorylation, causing an energy deficit contributing to impaired contractility. Better understanding of the mechanisms of this metabolic switching could be critical for reversing the condition.
Noninvasive Verification of a Very Small Intraocular Prostate Carcinoma Metastasis by 68Ga-PSMA-11 PET/CT
Authors: Ferdinand Ndum, Philipp Seifert, Martin Freesmeyer, Falk Gühne
Journal: Clinical Nuclear Medicine (2023)

A male patient underwent 68Ga-PSMA-11 PET/CT for the evaluation of a suspected intraocular metastasis in the right eye. Although the choroidal thickening was very small (4 × 2 mm), and ophthalmoscopy as well as MRI were inconclusive, PET/CT imaging showed distinct PSMA expression in the suspected lesion, confirming prostate cancer metastasis. The ability of dedicated PSMA ligand PET/CT imaging to detect small metastases, even with 68Ga-labeled ligands, has been demonstrated. Therefore, the use of further invasive diagnostic procedures could be avoided. Thus, the possibility of detecting intraocular metastases of prostate cancer should be considered in routine PET/CT imaging.
IFN-γ ELISpot-enabled machine learning for culprit drug identification in nonimmediate drug hypersensitivity
Authors: Yuda Chongpison, Sira Sriswasdi, Supranee Buranapraditkun, Pattarawat Thantiworasit, Pawinee Rerknimitr, Pungjai Mongkolpathumrat, Leena Chularojanamontri, Yuttana Srinoulprasert, Ticha Rerkpattanapipat, Kumutnart Chanprapaph, Wareeporn Disphanurat, Panlop Chakkavittumrong, Napatra Tovanabutra, Chutika Srisuttiyakorn, Chonlaphat Sukasem, Papapit Tuchinda, Padcha Pongcharoen, Jettanong Klaewsongkram
Journal: Journal of Allergy and Clinical Immunology (2023)
68Ga-PSMA-11 PET/CT in a Case of Isolated Parietal Peritoneal Metastasis From Prostate Adenocarcinoma
Authors: Qian Zhao, Aisheng Dong, Changjing Zuo
Journal: Clinical Nuclear Medicine (2023)

Abstract Isolated peritoneal metastasis of prostate cancer is extremely rare. We present 68 Ga-PSMA-11 PET/CT findings in a case of isolated parietal peritoneal metastasis from prostate adenocarcinoma 35 months after radical prostatectomy. The peritoneal metastases showed multifocal intense PSMA uptake, but subtle structural abnormalities on 68 Ga-PSMA-11 PET/CT. The patient was subsequently treated with androgen deprivation therapy. The peritoneal metastases progressed 25 months after the initiation of androgen deprivation therapy and were removed surgically. Histologic and immunohistochemical evaluation revealed metastatic prostate adenocarcinoma with treatment-related neuroendocrine differentiation. This case demonstrates the usefulness of 68 Ga-PSMA-11 PET/CT in identifying atypical metastasis from prostate adenocarcinoma.
Clinical Application of 18F-THK5351 PET to Identify Inflammatory Lesions Through Imaging Astrogliosis in a Case of Cytomegalovirus Ventriculoencephalitis
Authors: Keiko Hatano, Kenji Ishibashi, Kazuki Yamada, Kenji Ishii, Atsushi Iwata
Journal: Clinical Nuclear Medicine (2023)

18F-THK5351 PET is used to estimate the degree of astrogliosis. Because inflammatory lesions usually accompany astrogliosis, 18F-THK5351 PET is potentially worthy of clinical application in inflammatory disorders. Here, we report a case of cytomegalovirus ventriculoencephalitis in an immunocompromised 75-year-old woman who underwent 18F-THK5351 PET and conventional neuroimaging modalities, including 11C-methionine, 18F-FDG, and MRI. 18F-THK5351 PET was clearly superior to the other modalities in identifying inflammatory lesions and can therefore be a useful marker for identifying inflammatory lesions through imaging astrogliosis. This feature of 18F-THK5351 may contribute to the early diagnosis of cytomegalovirus ventriculoencephalitis.
Detailed Assessment of 18F-THK5351 Distribution Pattern in the Midbrain: Comparison With Progressive Supranuclear Palsy and Corticobasal Syndrome
Authors: Kenji Ishibashi, Masanori Kurihara, Ryoko Ihara, Mana Higashihara, Atsushi Iwata, Kenji Ishii
Journal: Clinical Nuclear Medicine (2023)

18F-THK5351 PET is used to image ongoing astrogliosis by estimating monoamine oxidase B levels. 18F-THK5351 preferentially accumulates around the substantia nigra (SN) and periaqueductal gray (PG) in the midbrain under healthy conditions and exhibits a "trimodal pattern." In progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), the midbrain 18F-THK5351 uptake can be increased by astrogliosis, collapsing the "trimodal pattern." We aimed to elucidate cases in which the "trimodal pattern" collapses in PSP and CBS.Participants in the PSP (n = 11), CBS (n = 17), Alzheimer disease (n = 11), and healthy control (n = 8) groups underwent 18F-THK5351 PET. Volumes of interest (VOIs) were placed on the SN, PG, and their midpoints. The midbrain uptake ratio (MUR) was calculated to assess the trimodal pattern as follows: MUR = (VOI value on the midpoint)/(VOI value on the SN and PG). Approximately, the trimodal pattern can be identified at MUR <1 but not at MUR >1.Compared with the healthy control group, MUR significantly increased in the PSP (P < 0.01) and CBS (P < 0.01) groups, but was unchanged in the Alzheimer disease group (P = 0.10). In the PSP group, all patients, including 2 with mild symptoms and a short disease duration, showed MUR >1. In the CBS group, MUR varied widely.In PSP, the trimodal pattern can collapse even in the early phase when symptoms are mild. In CBS, the trimodal pattern may or may not collapse depending on the underlying pathology.
Effective Reprogramming of Patient-Derived M2-Polarized Glioblastoma-Associated Microglia/Macrophages by Treatment with GW2580
Authors: Valentina Fermi, Rolf Warta, Amélie Wöllner, Catharina Lotsch, Lena Jassowicz, Carmen Rapp, Maximilian Knoll, Gerhard Jungwirth, Christine Jungk, Philip Dao Trong, Andreas von Deimling, Amir Abdollahi, Andreas Unterberg, Christel Herold-Mende
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Targeting immunosuppressive and pro-tumorigenic glioblastoma (GBM)-associated macrophages and microglial cells (GAM) has great potential to improve patient outcomes. Colony-stimulating factor-1 receptor (CSF1R) has emerged as a promising target for reprograming anti-inflammatory M2-like GAMs. However, treatment data on patient-derived, tumor-educated GAMs and their influence on the adaptive immunity are lacking. Experimental Design: CD11b+-GAMs freshly isolated from patient tumors were treated with CSF1R-targeting drugs PLX3397, BLZ945, and GW2580. Phenotypical changes upon treatment were assessed using RNA sequencing, flow cytometry, and cytokine quantification. Functional analyses included inducible nitric oxide synthase activity, phagocytosis, transmigration, and autologous tumor cell killing assays. Antitumor effects and changes in GAM activation were confirmed in a complex patient-derived 3D tumor organoid model serving as a tumor avatar. Results: The most effective reprogramming of GAMs was observed upon GW2580 treatment, which led to the downregulation of M2-related markers, IL6, IL10, ERK1/2, and MAPK signaling pathways, while M1-like markers, gene set enrichment indicating activated MHC-II presentation, phagocytosis, and T-cell killing were substantially increased. Moreover, treatment of patient-derived GBM organoids with GW2580 confirmed successful reprogramming, resulting in impaired tumor cell proliferation. In line with its failure in clinical trials, PLX3397 was ineffective in our analysis. Conclusions: This comparative analysis of CSF1R-targeting drugs on patient-derived GAMs and human GBM avatars identified GW2580 as the most powerful inhibitor with the ability to polarize immunosuppressive GAMs to a proinflammatory phenotype, supporting antitumor T-cell responses while also exerting a direct antitumor effect. These data indicate that GW2580 could be an important pillar in future therapies for GBM.
Impact of 18F-DCFPyL PET/MRI in Selecting Men With Low-/Intermediate-Risk Prostate Cancer for Focal Ablative Therapies
Authors: Adriano Basso Dias, Sangeet Ghai, Claudia Ortega, Seyed Ali Mirshahvalad, Nathan Perlis, Alejandro Berlin, Lisa Avery, Patrick Veit-Haibach, Theodorus van der Kwast, Ur Metser
Journal: Clinical Nuclear Medicine (2023)

To compare the diagnostic performance of multiparametric (mp) MRI to 18F-DCFPyL PET/MRI for detecting clinically significant (cs) prostate cancer (PCa) in men with low-/intermediate-risk PCa being considered for focal ablative therapy (FT), using 2 interpretation schemes, and to assess the rate of exclusion from FT for each modality.This prospective study evaluated men with low- or intermediate-risk PCa, potential candidates for FT based on initial biopsy as per institutional protocol, who underwent 18F-DCFPyL PET/MRI. Each modality (mpMRI, PET/MRI using PROMISE classification [PET/MRI PROMISE], and PET/MRI considering any focal lesion on PET as positive [PETFL/MRI]) was assessed independently. All suspicious lesions underwent PET/MRI-ultrasound fusion biopsies. Diagnostic performances were calculated and compared using the exact binomial test on paired proportions.Thirty-four men (median age, 64 years; interquartile range, 60-70 years) were included. Overall, 40 of 67 lesions (60%) identified on mpMRI and/or PET/MRI were malignant, and 34 of 40 lesions (85%) were csPCa (≥6 mm ISUP [International Society of Urological Pathology Grade Group] GG1 or ISUP-GG ≥2). On lesion-level analysis, for detecting csPCa, sensitivity appeared higher for PETFL/MRI than mpMRI and PET/MRI PROMISE (97% vs 76% and 79%, respectively [P = 0.02 and 0.03]), whereas specificity was lower (30% vs 85% and 88%, respectively [P < 0.001]). The calculated overall accuracy rates for PETFL/MRI, mpMRI, and PET/MRI PROMISE were 64%, 81%, and 84%, respectively. PETFL/MRI, mpMRI, and PET/MRI PROMISE excluded 10 of 34 (29%), 7 of 34 (21%), and 6 of 34 (18%) men from FT, respectively.18F-DCFPyL PET/MRI excluded nearly 30% of patients with low-/intermediate-risk PCa from FT, with a potential role in decreasing selection failure. Compared with mpMRI, PET/MRI had a higher sensitivity for detecting csPCa in men who were candidates for FT.ClinicalTrials.gov identifier NCT03149861.
Clinical and Genomic Landscape of FGFR3-Altered Urothelial Carcinoma and Treatment Outcomes with Erdafitinib: A Real-World Experience
Authors: Brendan J. Guercio, Michal Sarfaty, Min Yuen Teo, Neha Ratna, Cihan Duzgol, Samuel A. Funt, Chung-Han Lee, David H. Aggen, Ashley M. Regazzi, Ziyu Chen, Michael Lattanzi, Hikmat A. Al-Ahmadie, A. Rose Brannon, Ronak Shah, Carissa Chu, Andrew T. Lenis, Eugene Pietzak, Bernard H. Bochner, Michael F. Berger, David B. Solit, Jonathan E. Rosenberg, Dean F. Bajorin, Gopa Iyer
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Erdafitinib is the only FDA-approved targeted therapy for FGFR2/3-altered metastatic urothelial cancer. We characterized the genetic landscape of FGFR-altered urothelial carcinoma and real-world clinical outcomes with erdafitinib, including on-treatment genomic evolution. Experimental Design: Prospectively collected clinical data were integrated with institutional genomic data to define the landscape of FGFR2/3-altered urothelial carcinoma. To identify mechanisms of erdafitinib resistance, a subset of patients underwent prospective cell-free (cf) DNA assessment. Results: FGFR3 alterations predictive of erdafitinib sensitivity were identified in 39% (199/504) of patients with non-muscle invasive, 14% (75/526) with muscle-invasive, 43% (81/187) with localized upper tract, and 26% (59/228) with metastatic specimens. One patient had a potentially sensitizing FGFR2 fusion. Among 27 FGFR3-altered cases with a primary tumor and metachronous metastasis, 7 paired specimens (26%) displayed discordant FGFR3 status. Erdafitinib achieved a response rate of 40% but median progression-free and overall survival of only 2.8 and 6.6 months, respectively (n = 32). Dose reductions (38%, 12/32) and interruptions (50%, 16/32) were common. Putative resistance mutations detected in cfDNA involved TP53 (n = 5), AKT1 (n = 1), and second-site FGFR3 mutations (n = 2). Conclusions: FGFR3 mutations are common in urothelial carcinoma, whereas FGFR2 alterations are rare. Discordance of FGFR3 mutational status between primary and metastatic tumors occurs frequently and raises concern over sequencing archival primary tumors to guide patient selection for erdafitinib therapy. Erdafitinib responses were typically brief and dosing was limited by toxicity. FGFR3, AKT1, and TP53 mutations detected in cfDNA represent putative mechanisms of acquired erdafitinib resistance.
Clonal Hematopoiesis in Clinical and Experimental Heart Failure With Preserved Ejection Fraction
Authors: Jesse D. Cochran, Yoshimitsu Yura, Mark C. Thel, Heather Doviak, Ariel H. Polizio, Yuka Arai, Yohei Arai, Keita Horitani, Eunbee Park, Nicholas W. Chavkin, Anupreet Kour, Soichi Sano, Nitin Mahajan, Megan Evans, Mahalia Huba, Nadia Martinez Naya, Hanna Sun, Young Ho Ban, Karen K. Hirschi, Stefano Toldo, Antonio Abbate, Todd E. Druley, Frederick L. Ruberg, Mathew S. Maurer, Justin A. Ezekowitz, Jason R.B. Dyck, Kenneth Walsh
Journal: Circulation (2023)

Clonal hematopoiesis (CH), which results from an array of nonmalignant driver gene mutations, can lead to altered immune cell function and chronic disease, and has been associated with worse outcomes in patients with heart failure (HF) with reduced ejection fraction. However, the role of CH in the prognosis of HF with preserved ejection fraction (HFpEF) has been understudied. This study aimed to characterize CH in patients with HFpEF and elucidate its causal role in a murine model.
Bone Lipogranuloma Mimicking Metastatic Disease on 18F-FDG PET/CT
Authors: Selin Kesim, Fuat Dede, Emine Cesmecioglu, Damlanur Karaman, Halil Turgut Turoglu
Journal: Clinical Nuclear Medicine (2023)

Abstract Primary bone lipogranuloma is an extremely rare disease associated with reactive inflammatory granulomatous reaction associated with exogenous or endogenous lipids. Herein, we report a case of bone lipogranuloma with intense 18 F-FDG uptake, which mimics metastatic disease on 18 F-FDG PET/CT in a patient with breast cancer.
Evaluation of LAT1 Expression in Patients With Lung Cancer and Mediastinal Tumors
Authors: Tadashi Watabe, Naoko Ose, Sadahiro Naka, Eriko Fukui, Toru Kimura, Takashi Kanou, Soichiro Funaki, Hidetaka Sasaki, Takashi Kamiya, Kenta Kurimoto, Kayako Isohashi, Mitsuaki Tatsumi, Eku Shimosegawa, Hiroki Kato, Ryuichi Ohgaki, Yoshikatsu Kanai, Yasushi Shintani
Journal: Clinical Nuclear Medicine (2023)

Purpose of the Report L-type amino acid transporter-1 (LAT1) is a tumor-specific transporter expressed in various tumor types, with minimal expression in normal organs. We previously demonstrated 18 F-fluoro-borono-phenylalanine ( 18 F-FBPA) as a selective PET probe for LAT1 in a preclinical study. Herein, we evaluated LAT1 expression in preoperative patients with lung or mediastinal tumors using 18 F-FBPA PET and immunofluorescence staining. Patients and Methods The study population included patients with histopathological diagnosis (n = 55): primary lung cancers (n = 21), lung metastases (n = 6), mediastinal tumors (n = 15), and benign lesion (n = 13). PET scanning was performed 1 hour after the injection of 18 F-FBPA (232 ± 32 MBq). Immunofluorescence staining was performed on the resected tumor sections using LAT1 antibody. LAT1 staining was graded on a 4-grade scale and compared with the SUV max on 18 F-FBPA PET. Results A positive correlation was observed between the SUV max of 18 F-FBPA PET and LAT1 expression by immunofluorescence staining ( r = 0.611, P &lt; 0.001). The SUV max of 18 F-FBPA was 3.92 ± 1.46 in grade 3, 3.21 ± 1.82 in grade 2, 2.33 ± 0.93 in grade 1, and 1.50 ± 0.39 in grade 0 of LAT1 expression. Although 18 F-FBPA PET showed variable uptake in lung cancers and mediastinal tumors, benign lesions showed significantly lower SUV max than those in malignant lesions ( P &lt; 0.01). Conclusions Uptake on 18 F-FBPA PET reflected the expression level of LAT1 in lung and mediastinal tumors. It was suggested that 18 F-FBPA PET can be used for the precise characterization of the tumor in pretreatment evaluation.
18F-FDG PET/CT in a Patient With Epididymo-Testicular Malacoplakia
Authors: Xulong Zhao, Zaiying Long, Liming Yu, Xinjie Wang, Zhanli Fu
Journal: Clinical Nuclear Medicine (2023)

Abstract A 56-year-old man presented with a 2-month history of a mass in the right epididymo-testicular region, which exhibited heterogeneous high avidity for 18 F-FDG on PET/CT. Malignant tumor was highly suspected, leading to subsequent right orchiectomy and epididymectomy. Histopathological examination revealed the presence of characteristic Michaelis-Gutmann bodies within von Hansemann macrophages, confirming the diagnosis of malacoplakia.
Obesity is the main driver of altered gut microbiome functions in the metabolically unhealthy
Authors: Jacobo de la Cuesta-Zuluaga, Kelsey E. Huus, Nicholas D. Youngblut, Juan S. Escobar, Ruth E. Ley
Journal: Gut Microbes (2023)

Obesity (OB) and cardiometabolic disease are major public health issues linked to changes in the gut microbiome. OB and poor cardiometabolic health status (CHS) are often comorbid, which hinders efforts to identify components of the microbiome uniquely linked to either one. Here, we used a deeply phenotyped cohort of 408 adults from Colombia, including subjects with OB, unhealthy CHS, or both, to validate previously reported features of gut microbiome function and diversity independently correlated with OB or CHS using fecal metagenomes. OB was defined by body mass index, waist circumference, and body fat; CHS as healthy or unhealthy according to blood biochemistry and anthropometric data. We found that OB, more so than metabolic status, drove associations with gut microbiome structure and functions. The microbiome of obese individuals with and without co-existing unhealthy CHS was characterized by reduced metagenomic diversity, reduced fermentative potential and elevated capacity to respond to oxidative stress and produce bacterial antigens. Disease-linked features were correlated with increased host blood pressure and inflammatory markers, and were mainly contributed by members of the family Enterobacteriaceae. Our results link OB with a microbiome able to tolerate an inflammatory and oxygenated gut state, and suggest that OB is the main driver of microbiome functional differences when poor CHS is a comorbidity.
Right Adrenocortical Carcinoma Coexisting With Left Adrenal Sarcomatoid Carcinoma on FDG PET/CT
Authors: Haotian Chen, Jiaona Dai, Fabao Gao, Rong Tian
Journal: Clinical Nuclear Medicine (2023)

Abstract Bilateral adrenal glands synchronously involved by different types of pathologies are uncommon. An 80-year-old man underwent FDG PET/CT to evaluate bilateral adrenal masses, which were initially discovered by ultrasonography and confirmed by MRI. The images demonstrated elevated FDG activity in both lesions, which were subsequently diagnosed as concurrent right adrenocortical carcinoma and left adrenal sarcomatoid carcinoma respectively by histopathological examination.
EV-301 long-term outcomes: 24-month findings from the phase III trial of enfortumab vedotin versus chemotherapy in patients with previously treated advanced urothelial carcinoma
Authors: J.E. Rosenberg, T. Powles, G.P. Sonpavde, Y. Loriot, I. Duran, J.-L. Lee, N. Matsubara, C. Vulsteke, D. Castellano, R. Mamtani, C. Wu, M. Matsangou, M. Campbell, D.P. Petrylak
Journal: Annals of Oncology (2023)
Extracellular Perinexal Separation Is a Principal Determinant of Cardiac Conduction
Authors: William P. Adams, Tristan B. Raisch, Yajun Zhao, Rafael Davalos, Sarah Barrett, D. Ryan King, Chandra B. Bain, Katrina Colucci-Chang, Grace A. Blair, Alexandra Hanlon, Alicia Lozano, Rengasayee Veeraraghavan, Xiaoping Wan, Isabelle Deschenes, James W. Smyth, Gregory S. Hoeker, Robert G. Gourdie, Steven Poelzing
Journal: Circulation Research (2023)

Cardiac conduction is understood to occur through gap junctions. Recent evidence supports ephaptic coupling as another mechanism of electrical communication in the heart. Conduction via gap junctions predicts a direct relationship between conduction velocity (CV) and bulk extracellular resistance. By contrast, ephaptic theory is premised on the existence of a biphasic relationship between CV and the volume of specialized extracellular clefts within intercalated discs such as the perinexus. Our objective was to determine the relationship between ventricular CV and structural changes to micro- and nanoscale extracellular spaces.
Intravenous Pyogenic Granuloma in the Inguinal Canal Mimicking Lymph Node Metastasis on PSMA PET/CT
Authors: Sarah MD. Skyum, Andrea K. Anthonsen, Giedrius Salkus, Dmitry Kvon, Helle D. Zacho
Journal: Clinical Nuclear Medicine (2023)

Abstract We present a 68-year-old man with newly diagnosed high-risk prostate cancer who was referred for PSMA PET/CT after the initial CT showed a contrast-enhanced structure resembling a lymph node in the left inguinal canal. No other findings suggesting metastatic disease were seen on CT or bone scintigraphy. PSMA PET/CT showed moderate PSMA uptake in the inguinal tissue, substantiating an unexpected location of lymph node metastasis. The uncommon location warranted an excision biopsy, and an IV pyogenic granuloma was diagnosed on histological examination, emphasizing the importance of biopsy of unexpected findings.
Epoxyeicosatrienoic Acids Prevent Cardiac Dysfunction in Viral Myocarditis via Interferon Type I Signaling
Authors: Zhou Zhou, Min Zhang, Chengcheng Zhao, Xu Gao, Zheng Wen, Junfang Wu, Chen Chen, Ingrid Fleming, Jiong Hu, Dao Wen Wang
Journal: Circulation Research (2023)

Myocarditis is a challenging inflammatory disease of the heart, and better understanding of its pathogenesis is needed to develop specific drug therapies. Epoxyeicosatrienoic acids (EETs), active molecules synthesized by CYP (cytochrome P450) enzymes from arachidonic acids and hydrolyzed to less active dihydroxyeicosatrienoic acids by sEH (soluble epoxide hydrolase), have been attributed anti-inflammatory activity. Here, we investigated whether EETs have immunomodulatory activity and exert protective effects on coxsackie B3 virus-induced myocarditis. Viral infection altered eicosanoid epoxide and diol levels in both patients with myocarditis and in the murine heart and correlated with the increased expression and activity of sEH after coxsackie B3 virus infection. Administration of a sEH inhibitor prevented coxsackie B3 virus-induced cardiac dysfunction and inflammatory infiltration. Importantly, EET/sEH inhibitor treatment attenuated viral infection or improved viral resistance by activating type I IFN (interferon) signaling. At the molecular level, EETs enhanced the interaction between GSK3β (glycogen synthase kinase-3 beta) and TBK1 (TANK-binding kinase 1) to promote IFN-β production. Our findings revealed that EETs and sEH inhibitors prevent the progress of coxsackie B3 virus-induced myocarditis, particularly by promoting viral resistance by increasing IFN production.